The present invention relates to a local delivery device for the delivery of a therapeutic agent to a hollow tubular organ. More specifically the present invention relates to a multi-balloon catheter with an adjustable inter-balloon distance, adapted for delivery of a therapeutic agent to one or more variable lengths of a hollow organ segment.
Vascular and lumenal catheters are widely used in medicine to treat a variety of vascular and lumenal diseases. In some instances, a catheter comprising an inflatable element such as a balloon is used to physically remove deposits on the interior of a tissue lumen. In other instances a catheter is used to deliver a therapeutic agent to a diseased portion of a tissue lumen. There are also catheters which combine inflatable elements and therapeutic agent delivery systems with the aim of treating diseased vessels.
Several recent catheter descriptions pertain to the use of dual-balloon catheters that when inflated define a sealed space suitable for the delivery of a drug or other therapeutic agent. In the catheter designs, the space between the two balloons is fixed. For example, U.S. Pat. No. 5,320,604 to Baxter-International Inc, discloses a single-lumen balloon catheter for embolectomy, dilation, occlusion and infusion of treatment fluids. The catheter shaft comprises a pair of expandable balloons spaced apart on the catheter. Located between the catheters is an infusion section comprising a perforation in fluid communication with the lumen of the catheter. Drugs or other treatment fluids may be delivered via the infusion section to the occluded region of the diseased tissue lumen. Analogous designs are provided for in U.S. Pat. No. 5,460,610 and U.S. Pat. No. 5,380,284. A three balloon catheter is disclosed in U.S. Pat. No. 5,176,638.
Similarly, U.S. Pat. No. 4,824,436 to Wolinsky describes a process for local administration of heparin and other agents to inhibit arterial smooth muscle cell proliferation using a catheter. The catheter contemplated in U.S. Pat. No. 4,824,436 comprises a proximal balloon and a distal balloon separated by a fixed distance. Located on the catheter, in between the two balloons is a perforation which is connected to an infusion lumen in the catheter. Heparin or other agents may be delivered through the catheter lumen to a vascular segment which has been occluded by inflation of both balloons. Also disclosed in the invention is the optional presence of a third balloon located in between the proximal and distal balloons referred to previously. The third balloon may be used to treat plaque deposits in vascular structures. After the middle balloon is deflated the proximal and distal balloons are expanded to create a chamber around the angioplasty site for the delivery therapeutic materials such as heparin. Following delivery of therapeutic material, the balloons are deflated and the catheter is removed. U.S. Pat. No. 5,662,609 relates to a catheter and a technique for treating diseased portions of tissue lumens by the introduction of at least one therapeutic agent at the diseased region. A catheter is positioned in a lumen such that a first and a second expansile member surrounds a diseased portion of tissue. Both expansile members are inflated to occlude the diseased region. A therapeutic agent is introduced into the occluded region of the diseased tissue lumen from a perfusion port located between the two expansile members. The catheter may also have other expansile members located in between, or outside of the first two expansile members. For example, a third expansile member may be provided between the first two expansile members. The inflation of the third member may function as an angioplasty balloon or other disruptive means. The devices disclosed in U.S. Pat. No. 4,824,436 and U.S. Pat. No. 5,662,609 require a plurality of lumens which increases the diameter of the catheter and therefore limits their use to hollow tubular organs of substantial cross section.
In U.S. Pat No. 5,817,113 to Heartport Inc, a drug delivery catheter which has a distal balloon and a proximal balloon separated by a few centimeters distance along the catheter shaft is disclosed. The catheter may have a single inflation lumen which connects to both balloons or separate inflation lumens. The catheter may also be provided with a flushing lumen which connects to a flushing port located on the catheter shaft for flushing of the site with saline to improve visibility of the structure. It is also disclosed that the catheter has a perfusion lumen for blood flow through the catheter. Drugs or other therapeutic molecules may be delivered via a lumen of the catheter to the drug delivery port on the catheter shaft located between the inflated balloons. U.S. Pat. No. 5,090,960, teaches the use of an offset two-catheter, two-balloon system. One catheter comprises a delivery port, and he other catheter a withdrawal port. One eccentric balloon is attached to each of the two catheters, and when inflated, these balloons push each of the catheters against the wall of the vessel. This catheter also provides openings on either side of the balloons, outside the isolated region, for the perfusion of blood through one of the catheters to ensure blood flow when the balloons are inflated.
U.S. Pat. No. 5,855,546 to Sci-Med Life Systems discloses a catheter device capable of simultaneous irradiation of blood vessels, angioplasty and drug infusion. The catheter is equipped with a helical perfusion balloon which when inflated defines a perfusion lumen which facilitates blood flow through the occluded artery portion. The catheter also comprises a lumen with perforations interspersed between the balloon windings to provide a confined volume for delivery of drugs to the vessel wall alone or in combination with radiation therapy.
U.S. Pat. No. 5,704,908 to Genetronics discloses an electroporation catheter for introducing molecules into cells at selected locations within a endoluminal structure. One embodiment comprises a pair of balloons spaced apart at a fixed distance on a guidewire. Each balloon comprises a separate electrode coating which in operation promotes electroporation of drugs or genes trapped or confined to the inter-balloon space into the cells of the endoluminal structure.
The above catheters provide for the delivery of a therapeutic agent to an isolated portion of a vascular segment, thereby permitting the treatment of the vessel lumen with one or a combination of therapeutic modalities, for instance, radiation, drugs, or genetic constructs. However, in all of these devices, the inter-balloon distance is fixed and the length of the vessel lumen which may be perfused with drugs is limited by the distance between the occluding balloons in the catheter structure.
U.S. Pat. No. 5,820,595 discloses an adjustable dual balloon catheter, however, there is no teaching that this catheter may be used as a local delivery device.
U.S. Pat. No. 5,919,163 relates to a dual balloon catheter with openings along the catheter stem located there between. The perforations along the catheter stem function to remove contaminated blood from the body. This catheter is used to isolate a region of interest and withdraw contaminated blood for further processing. The inter-balloon spacing of this catheter is adjustable, however the spacing is determined prior to insertion within the blood vessel. There is no teaching of drug delivery using this dual balloon catheter.
U.S. Pat. No. 5,342,306 discloses an adjustable dual balloon catheter, that comprises one perforation adjacent to a diffusable barrier that permits the supply of an agent within the isolated region between the two balloon portions. The one diffusion port is located at a fixed distance along the catheter, irrespective of the inter-balloon distance. With an increase in inter-balloon distance, the diffusion rate of any supplied agent within the isolated region would be low, requiring long insertion times for adequate diffusion of the medicament within the isolated region. Perfusion ports that direct blood flow through the catheter, and around the balloons, permit the catheter to remain within a physiological passage for prolonged treatment periods. There is also no disclosure of any mechanism providing for precise adjustment or measurement of the inter-balloon distance while the catheter is inserted in situ. An analogous catheter is disclosed in U.S. Pat. No. 4,655,746, comprising a single infusion port located at the rear of the proximal balloon at one end of the isolated region. The inter-balloon distance within this catheter is determined using contrasting material. No mechanism is disclosed for fine adjustment of the inter-balloon distance when in use.
U.S. Pat. No. 5,462,529 discloses a complex dual balloon catheter comprising three overlapping catheter sleeves, a first sleeve associated with the distal balloon, the second attached to a burden loosening member capable of rotating about the first sleeve, and the third attached to a proximal balloon. The space between the second and first catheter sleeves may be used to introduce a fluid of interest within the inter-balloon region (a single port design). The lumen between the second and third catheter may be used for the removal of blood and other components from the blood vessel loosened by the burden loosening member along with the fluid of interest which aids in flushing the isolated region. There is no method or mechanism disclosed for adjusting the inter-balloon distance when the catheter is in use.
To effect radiation and drug delivery to a long vessel segment, either a multitude of catheters must be available with different lengths of inter-balloon distances and infusion ports, or the catheter must be repositioned within the vascular element to treat adjacent lumenal tissue. Similarly, treatment of hollow tubular organs with localized diseased areas using catheters that infuse a therapeutic agent to a larger than required region may also be undesirable. In the case of adjustable catheters, mechanisms providing for accurate and easy adjustment while in use, is needed, as are catheters that comprise infusion port designs permitting ready delivery of a drug to an isolated region, irrespective of the length of the isolated region. Therefore, there is a need within the art for a multi-balloon catheter that provides for an easily adjustable inter-balloon distance in situ, to optimize the isolation of a diseased hollow organ portion, and provides for the delivery of a therapeutic agent to this isolated area.
It is an object of the invention to overcome defects in the prior art.
The above object is met by the combination of features of the main claims. The sub-claims further disclose further advantageous embodiments of the invention.
The present invention relates to a local delivery device for the delivery of a therapeutic agent to a hollow tubular organ. More specifically the present invention relates to a multi-balloon catheter with an adjustable inter-balloon distance, adapted for delivery of a therapeutic agent to one or more variable lengths of a hollow organ segment.
The present invention relates to a local delivery device for the administration of a liquid of interest comprising:
i) a distal catheter unit comprising a distal occluding balloon in communication with a distal occluding inflation port, a distal catheter shaft comprising a plurality of infusion ports distributed within the distal catheter shaft and in fluid communication with a liquid of interest delivery port;
i) a proximal catheter unit, comprising a proximal occluding balloon in communication with a proximal occluding inflation port, and a proximal catheter shaft, the proximal catheter shaft is slidable over the distal catheter shaft; and
iii) an adjustment mechanism for setting a distance between the distal occluding balloon and the proximal occluding balloon.
The present invention is also directed to a local delivery device as defined above, wherein the adjustment mechanism is selected from the group consisting of a threaded screw adjustment mechanism, a rack and pinion adjustment mechanism, a toothed displacement mechanism, a hydraulic regulated displacement mechanism, a compressed air regulated displacement mechanism, a frictional slide adjustment mechanism, a motor drive adjusted mechanism, and an automatic pull back adjustment mechanism, the adjustment mechanism interacting with either the distal catheter shaft, the proximal catheter shaft, or both the distal and proximal catheter shafts. Actuating the adjustment mechanism causes the proximal catheter shaft or the distal catheter shaft to move relative to each other, and thereby adjust the number of exposed infusion ports.
The present invention also pertains to the local delivery device as defined above, further comprising a quantifying device for determining the distance between the distal occluding balloon and the proximal occluding balloon.
The present invention also pertains to the local delivery device as defined above wherein a valve element, comprising an xe2x80x9cOxe2x80x9d ring hemostatic valve, is associated with the adjustment mechanism. The adjustment mechanism may also be a threaded screw adjustment mechanism, or a frictional slide adjustment mechanism.
The present invention also embraces the local delivery device as defined above, wherein the distal catheter unit further comprises a lumen traversing the terminal portion of the distal catheter shaft and capable of receiving a guidewire. It is also contemplated that a lumen traversing the entire length of the distal catheter shaft, may receive a guidewire.
This invention also pertains to the local delivery device as defined above, wherein the proximal catheter shaft comprises within its inner surface a sealing element, the sealing element capable of forming a seal between the proximal catheter shaft and the distal catheter shaft thereby sealing the infusion ports residing within the proximal catheter shaft.
This invention also considers a method of administering a therapeutic agent to a hollow tubular organ comprising:
i) inserting the local delivery device defined above within the hollow tubular organ;
ii) inflating one or both of the distal and proximal occluding balloons;
iii) inflating the other of the distal or proximal occluding balloons to produce an occluded space;
iv) evacuating or flushing the occluded space; and
v) introducing the therapeutic agent into the occluded space.
It is also contemplated that after steps i) or ii), there follows a step of actuating the adjustment mechanism to alter the distance between the proximal and distal occluding balloons.
The present invention also relates to the above method, wherein the step of introducing, step iv), involves introducing the therapeutic agent under pressure, or via electroporation.
The present invention includes the above method, wherein the therapeutic agent is selected from the group consisting of a drug, a nucleotide sequence encoding a protein of interest, and a construct comprising a nucleotide sequence encoding a protein of interest. The therapeutic agent may be administered within a liposome, or as an emulsion, microemulsion or along with a cationic lipid. Furthermore, the nucleotide sequence or the construct comprising a nucleotide sequence may be administered within a bacterial, or viral vector.
The present invention is also directed to the method as defined above wherein the therapeutic agent is a photoactivated therapeutic agent, and the local delivery device further comprises one or more fibre optic strands directing light from a light source to a treatment site, thereby activating the photoactivated compound.
The present invention also provides for the method as defined above wherein the therapeutic agent is an antithrombic therapeutic agent or a radio-sensitized therapeutic agent, and the local delivery device further comprises a radioactive source.
The present invention also embraces a method of measuring an inter-balloon distance in a local delivery device when the local delivery device is inserted within a subject, comprising measuring the inter-balloon distance using a graduated scale.
The local delivery device of the present invention permits a variety of inter-catheter balloon distances to be established even while the local delivery device is inserted within a hollow tubular organ. By regulating the distance between a proximal and distal catheter balloon, the administration of a therapeutic agent or liquid of interest can be targeted to a specific site and minimise the exposure of non diseased tissue to the therapeutic agent. Furthermore, by providing a plurality of ports within the catheter, the fluid of interest can be readily administered to the treatment site. In doing so, shorter delivery times, and more uniform delivery may be achieved. As a result of the efficient delivery of a liquid of interest to a treatment site, ports to permit distal perfusion of the hollow organ may not be required for some applications, therefore, the overall diameter of the catheter can be reduced. This simplified design permits use of the local delivery device of the present invention within smaller hollow tube organs than can be achieved using current catheter designs.
This summary of the invention does not necessarily describe all necessary features of the invention but that the invention may also reside in a sub-combination of the described features.